The Women's Health Initiative clinical trial of estrogen plus progestin for the prevention of cardiovascular disease in healthy, postmenopausal women, which was recently stopped due to adverse effects, as well as other secondary prevention clinical trials, have found increased risk of stroke in users of estrogen plus progestin. We wish to investigate possible mechanisms for such an increase by studying biomarkers of hemostasis /inflammation as risk factors for ischemic stroke and as mediators of stroke related effects of hormone replacement therapy and other risk factors, including hypertension and lifestyle variables. The goal of the proposed study is to determine whether blood-based biomarkers related to systemic inflammation, and/or atherothrombosis/hemostasis/coagulation may be important risk factors for ischemic stroke and subtypes of ischemic stroke among older women. We will conduct a population based nested case-control study of 1050 ischemic stroke cases and 1050 matched controls among participants in the Observational Study component of the Women's Health Initiative (WHI-OS). The WHI-OS, conducted in a multi-ethnic cohort in 40 centers throughout the United States, is a prospective study of 93,676 postmenopausal women, followed for 8 to 12 years, with extensive baseline and follow-up data including blood and DNA specimens collected and stored at baseline. Multivariate modeling techniques will be used to investigate the associations of selected biomarkers, hypertension, hormone use and lifestyle variables, with risk of ischemic stroke and specific stroke subtypes as classified by central adjudicators. We will also determine whether the effects on stroke risk of established risk factors (hypertension, smoking, diabetes) and use of specific medications (statins, aspirin, non-steroidal anti-inflammatory agents, estrogen and progesterone) will be modified in the presence of markers of inflammation and/or of atherothrombosis/hemostasis.